The present invention relates to radiolabeled compounds, their method of making, and their method of use in clinical nuclear medicine. More specifically, the present invention relates to a novel compound, iodinated 4-amino-3-iodobenzylguanidine which in radioiodinated form can be used in a radiopharmaceutical composition as an imaging agent, particularly for the heart, adrenal medulla, and tumors of the adrenal medulla as well as a treatment agent for tumors of the adrenal medulla. The present invention also relates to a method of synthesis and a kit for synthesis of the radioiodinated compound of this invention.
Radiolabeled compounds which are subject to localization in particular organs or tumors therein are of great value for diagnosis and/or therapeutic purposes for diseases of the human body. For example, Thallium-201 and fatty acids labeled with carbon-11 and iodine-123 have been utilized as heart imaging agents. Also, various phosphonate ligands labeled with technetium-99m have been used to image infarcted regions of the heart. However, although many useful radiolabeled compounds are known, there remains a need for the discovery of improved compounds which are effective for routine imaging of particular organs, tissues, or tumors therein. In addition, there remains a need for radiolabeled compounds which are useful in treating tumors of specific organs of the human body.
The agent meta-iodobenzylguanidine labeled with iodine-131 or iodine-123 has been found to image the adrenal medulla and tumors of the adrenal medulla and is disclosed in copending U.S. patent application of Wieland, et al., Ser. No. 250,059 filed Apr. 1, 1981 for "Imaging Agent and Method of Use", as well as in articles cited therein and in Lynn, et al., "Portrayal of Pheochromocytoma and Normal Human Adrenal Medulla by M-[.sup.123 I] Iodobenzylguanidine: Concise Communication", J. Nucl. Med. 25:436-440, 1984. There remains a need, however, for an agent which can be more easily synthesized in radioiodinated form than radioiodinated meta-iodobenzylguanidine.
There also remains a need for an improved imaging agent for the heart. The above-mentioned radioiodinated meta-iodobenzylguanidine gives images of the heart but the synthetic difficulty and general unavailability of this agent have limited its clinical use. Furthermore, it would be desirable to have an imaging agent having a higher degree of selectivity for the adrenergic nerves of the heart than radioiodinated meta-iodobenzylguanidine. Thallium-201 is used for heart imaging, but it is expensive and has less than optimum nuclear imaging properties. Carbon-11 fatty acids can be used for heart imaging but their use is severely limited by the requirement for an in-house cyclotron for the product of the short-lived isotope (T1/2=20 min) C-11. The use of iodine-123 fatty acids is still being evaluated in various nuclear medicine clinics throughout the world, but these compounds have a short biologic T1/2 (about 10 minutes) in the heart. Technetium-99m labeled disphosphonates are useful heart imaging agents but are not heart perfusion agents and are limited to imaging only severely damaged or infarcted regions of the heart.
In accordance with the present invention, a novel iodinated compound is provided. The novel iodinated compound can be synthesized in radioiodinated form, and can be readily synthesized by means of the kit and method of synthesis of this invention. A radiopharmaceutical composition comprising the radioiodinated compound can be used as an exceptional imaging agent, particularly for the adrenal medulla, tumors of the adrenal medulla and the heart. The radioiodinated compound has a high degree of selectivity for the adrenergic nerves of the heart. A radiopharmaceutical composition comprising the radioiodinated compound can also be used for the diagnosis and/or treatment of tumors, particularly tumors of the adrenal medulla.